Aug 2026· Frontiers in Bioengineering and Biotechnology· Vol 14· 0 citations· 38 references
Medicine
TL;DR
By systematically removing host restriction factors, this platform provides a versatile and powerful strategy for accelerating viral propagation, offering a strong foundation for more efficient development and large-scale production of cell culture-based anti-viral vaccines.
Abstract
The efficiency of cell culture-based vaccine production is fundamentally constrained by the antiviral defenses of host cells, creating a major bottleneck for rapid and large-scale vaccine manufacturing. Key antiviral proteins-such as RNase L, PKR, and JAK1 act as intrinsic brakes on viral replication, limiting efficient propagation of many clinically relevant viruses. To overcome this challenge, we generated HEK293T, Vero, and MDCK cell lines with targeted knockouts of multiple antiviral genes. Notably, these engineered cells maintained normal growth and viability while supporting markedly increased viral yields. Multi-gene deletions enhance the replication of both enveloped viruses, including influenza A virus, pseudotyped lentivirus, and porcine epidemic diarrhea virus (PEDV), and non-enveloped viruses such as coxsackievirus. The magnitude of enhancement scaled proportionally with the number of genes disrupted. By systematically removing host restriction factors, this platform provides a versatile and powerful strategy for accelerating viral propagation, offering a strong foundation for more efficient development and large-scale production of cell culture-based anti-viral vaccines.
A modular, helper-virus-free and high-efficiency rescue platform based on an orthogonal transcription system utilizing orthogonal promoters and engineered RNA polymerases fused to an mRNA capping enzyme is developed and provides a proof-of-concept methodological framework for the rapid development of vaccine candidates.
Zihan Ma, Weijun Wang, Qiuli Lou et al.· Synthetic and Systems Biotec...· 0 citations
The combination knockout of CCR5, MOGS, and viral sequences profoundly reduces HIV-1 replication in an ex vivo cellular model, that is, HIV-1-infected peripheral blood mononuclear human cells, thus offering a pathway to launch further preclinical studies.
Z. Safaei, Anna Bellizzi, Hong Liu et al.· Human Gene Therapy· 0 citations
This review systematically summarize recent progress in CRISPR/Cas9-based screening studies of major livestock and poultry viruses, including foot-and-mouth disease virus (FMDV), swine enteric coronaviruses, African swine fever virus (ASFV), porcine reproductive and respiratory syndrome virus (PRRSV), avian leukosis virus (ALV), and other zoonotic pathogens.
Influenza A virus (IAV) remains a major threat to human and animal health, highlighting the need for efficient approaches to identify host factors and antivirals. Reporter viruses are critical tools for these efforts, but incorporating large reporter genes often compromises viral fitness and genetic stability. Here, we developed a replication competent reporter IAV by fusing an 11-amino acid HiBiT tag into the nonstructural protein 1 (NS1) of the A/WSN/1933 (H1N1) backbone. The modified virus retained parental virion morphology, comparable replication kinetics, and in vivo tissue tropism, while enabling the highly sensitive, rapid, and quantitative detection of viral replication. Using this reporter virus, we established a robust high-throughput screening (HTS) platform with excellent assay quality and validated its capability to identify host regulators of IAV infection. Application of this platform to host-encoded micropeptides (miPEPs) led to the identification of cytokine-inhibitory micropeptide 53 (CIM53) as a novel regulator of IAV replication. Mechanistically, CIM53 promoted IAV replication by intrinsically suppressing antiviral innate immune responses. Furthermore, although CIM53 enhanced viral replication, its immunomodulatory activity contributed to reduced lung injury and improved survival when combined with Oseltamivir (OSV) treatment in infected mice. Our study establishes a highly practical screening platform for virological research and highlights CIM53 as a potential host-directed adjunct therapy for severe IAV Infection.
This review comprehensively evaluates the rational design of classical animal herpesvirus vectors, including pseudorabies virus, herpesvirus of turkeys, and feline herpesvirus type 1, providing perspectives on how continuous biotechnological innovations will empower herpesvirus vectors to serve as formidable prophylactic tools against emerging and re-emerging infectious diseases.
Jia-Hui Guo, Chen Mei, Xin-Yao Sun et al.· Frontiers in Microbiology· 0 citations
This review systematically summarizes the evolution, technical framework and optimization strategies of RNA virus reverse genetics, with three prototype viruses covering all major RNA genome types: SARS-CoV-2 (+ssRNA), non-segmented negative-sense Newcastle disease virus (NDV), and segmented negative-sense influenza A virus.
Yu Guo, Ting Xue, Jianhua Wang et al.· Frontiers in Virology· 0 citations
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